Production of Erythropoietin by Anoxic Perfusion of the Isolated Kidney of a Dog

Zangheri, Elena; Campana, H.; Ponce, F.; Silva, J. C.; Fernandez, Fidel; Rodríguez, Julián

doi:10.1038/199572a0

Cited by 27 publications

(9 citation statements)

References 8 publications

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“…Our findings agree with and extend previous observations that the isolated perfused kidney releases erythropoietin (EPO) in an oxygen-dependent manner [7,9,16,28]. Our data show that hypoxia-induced stimulation of EPO release is a phenomenon that is not just restricted to isolated perfused kidneys taken from hypoxic animals [7] but is also observed with kidneys taken from normoxic rats [9,16,28].…”

Section: Discussionsupporting

confidence: 92%

“…Our data show that hypoxia-induced stimulation of EPO release is a phenomenon that is not just restricted to isolated perfused kidneys taken from hypoxic animals [7] but is also observed with kidneys taken from normoxic rats [9,16,28]. Since the normoxic rat kidney contains no stores for EPO [13] one can infer that the isolated perfused rat kidney is capable of de novo synthesis of EPO.…”

Section: Discussionmentioning

confidence: 64%

“…A strong argument for an oxygen-sensing function of the kidney would be the demonstration that the isolated kidney is capable of producing EPO in an oxygen-dependent manner, as is known to occur in the intact organism. In fact, it has been reported that isolated perfused kidneys release more EPO when the oxygen supply is lowered [7,9,16,28]. In those studies the amount of EPO released from isolated kidneys was determined indirectly either by measuring EPO dependent 59Fe incorporation into red blood cells [7,9,28] or by determination of the proliferative activity of the erythron [16].…”

Section: Introductionmentioning

confidence: 99%

“…In fact, it has been reported that isolated perfused kidneys release more EPO when the oxygen supply is lowered [7,9,16,28]. In those studies the amount of EPO released from isolated kidneys was determined indirectly either by measuring EPO dependent 59Fe incorporation into red blood cells [7,9,28] or by determination of the proliferative activity of the erythron [16]. Moreover, those experiments were partly performed in kidneys isolated from hypoxic animals, a fact that makes it difficult to distinguish whether EPO formation had been really induced or had merely been modulated during ex vivo perfusion [7].…”

Section: Introductionmentioning

confidence: 99%

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Oxygen-dependent erythropoietin production by the isolated perfused rat kidney

et al. 1991

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Abstract. In this study we have investigated the role of oxygen delivery and of classic second messengers on erythropoietin production by the isolated perfused rat kidney. We found that the rat kidney was capable of de novo synthesis of erythropoietin. The erythropoietin production rate was inversely related to the oxygen pressure in the perfusate and increased from 0.17 to 1.85U erythropoietin h -1 g kidney -z when arterial PO2 was lowered from 500 mmHg to 30 mmHg. Addition of forskolin (10 gM) and 8-bromo-cGMP (100 gM) to the perfusate elicited significant effects on the renal vascular resistance, but had no significant effect on erythropoietin production. Hypoxia-induced erythropoietin formation, however, was blocked by calmidazolium (1 gM) and W-7 (10 lxM), two structurally different putative calmodulin antagonists. Calmidazolium and W-7 had no effect on other functional parameters of the isolated perfused rat kidney such as flow rate, glomerular filtration rate or sodium reabsorption. Our findings suggest that the oxygensensing mechanism that controls renal erythropoietin production is primarily located in the kidney itself. A cap cium/calmodulin-dependent cellular reaction could be involved in the signal transduction process.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxygen-dependent erythropoietin production by the isolated perfused rat kidney

et al. 1991

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“…Erslev had contended that erythropoietic material is released only from injured and disintegrating renal tissue but not from well-preserved and metabolically active kidneys (20). Our finding (18) and the work of Kuratowska et al (19) were confirmed by Reissmann & Nomura (22) and Zangheri et al (23) and were most helpful in expelling doubts by some investigators that the kidney produced Epo. Interestingly, a few years later, Erslev also reported that isolated rabbit kidneys perfused with serum-free medium alone triggered kidney production of Epo (24).…”

Section: Early Work On Cobaltsupporting

confidence: 86%

A Quest for Erythropoietin Over Nine Decades

Fisher

1998

Annu. Rev. Pharmacol. Toxicol.

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The major research accomplishments of the author are described from the time of his PhD thesis work on the mechanism of cobalt polycythemia to the present day. His early work on the quest for the cell that produces erythropoietin (Epo) to his current work on oxygen sensing and signal transduction pathways involved in erythropoietin gene expression are reported. He describes his main research interest in the mechanism of cobalt polycythemia between 1954 and 1962 and his research on how hormones such as the glucocorticoids function in the regulation of erythropoiesis (1956)(1957)(1958)(1959)(1960)(1961)(1962). His major findings during this period were the discovery that hydrocortisone and corticosterone stimulated erythropoiesis (1958) and that cobalt increased erythropoietin production in the isolated perfused dog kidney (1961). He describes how he was led astray in some of his early studies on the cells in the kidney that produce erythropoietin, because of the less-developed technology available to him at that time; and how in situ hybridization and other molecular biology techniques enabled him to confirm some of the earlier work in mice by other investigators that interstitial cells in the kidney were the site of production of erythropoietin in the primate. His work in the controversial area of the mechanism of the anemia of end-stage renal disease is described in detail, as it pertains to Epo deficiency and suppressed erythroid progenitor cell response to Epo. He also discusses his recent work on signal transduction pathways (hypoxia, nitric oxide, adenosine, and C kinase) in oxygen sensing and Epo gene expression. Early EducationI was born in Tucapau (now Startex), South Carolina, in 1925. Tucapau was a textile mill town that enjoyed both hydroelectric and steam (generated by coalburning furnaces) power to run the mill. My father was attracted to Tucapau to play on their textile league baseball team because he was an outstanding baseball 1 0362-1642/98/0415

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Regulation of Erythropoietin Production

Fisher

1992

Comprehensive Physiology

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The sections in this article are: Physicochemical Properties of Erythropoietin Assay and Standardization of Erythropoietin Model for Kidney Production of Erythropoietin Renal Site of Production of Erythropoietin Extrarenal Erythropoietin Production Sites of Action of Erythropoietin Anemia of Renal Insufficiency Erythropoietin and Polycythemia Pharmacological Agents that Influence Erythropoietin Production Pharmacokinetics of Erythropoietin Potential Therapeutic uses of Erythropoietin Summary

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Production of Erythropoietin by Anoxic Perfusion of the Isolated Kidney of a Dog

Cited by 27 publications

References 8 publications

Oxygen-dependent erythropoietin production by the isolated perfused rat kidney

Oxygen-dependent erythropoietin production by the isolated perfused rat kidney

A Quest for Erythropoietin Over Nine Decades

Regulation of Erythropoietin Production

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